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Purpose: Five patients who underwent uncomplicated retinal pigment epithelium (RPE)-choroid transplantation for neovascular age-related macular degeneration developed a destructive inflammatory reaction causing subretinal fluid accumulation and extensive RPE atrophy in the graft. We hypothesized that this inflammation could be caused by an auto-immune response against the graft, resulting in circulating auto-antibodies. The aim of our study was to examine a potential autoimmune origin, which would allow a more targeted therapy approach. Methods: Five above-mentioned patients and four control groups of five patients each were included: 1) after uncomplicated RPE-choroid transplantation, 2) after full macular translocation, 3) treated with anti-vascular endothelial growth factor, and 4) healthy controls. Histopathology of rejected graft tissue was performed using standard procedures. Presence of RPE-choroid autoantibodies in serum was examined by indirect immunofluorescence and Western blot, and human leukocyte antigen (HLA) typing was performed. Results: Histopathological examination of an explanted graft showed infiltration of T-lymphocytes and macrophages in the choroid and RPE, and an increased number of B-cell lymphocytes were found in the choroid. Indirect immunofluorescence showed weak RPE-choroid autoantibody immunoreactivity in three patients of different groups. Western blot did not show specific RPE-choroid autoantibody immunoreactivity and no difference of HLA genotypes between the groups was found. Conclusions: Although local mononuclear inflammatory cell infiltration and a high number of B-lymphocytes were observed in an explanted graft, we did not detect serological evidence of an autoimmune origin of the postoperative inflammation using direct immunofluorescence and Western Blot. Alternatively, the graft failure may have been caused by local innate inflammation, triggered by breakdown of tolerance. Based on our current findings of this small study group, we have no rationale to pursue therapies targeted towards autoreactive graft failure. More research is needed to confirm our findings.
van Romunde, S. H. M., Vergouwen, D. P. C., Iacovello, D., Roelen, D. L., Verdijk, R. M., ten Berge, J. C. E. M., … van Meurs, J. C. (2022). Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response. Journal of Ophthalmic Inflammation and Infection, 12(1). https://doi.org/10.1186/s12348-022-00305-2